ABSTRACT
The azoopsermia factor c (AZFc) region of human Y-chromosome is an essential genomic segment for spermatogenesis with frequent non-allele homologous recombination (NAHR). Recent case-control studies on the association of the NAHR-based AZFc structural mutations with spermatogenic failure produced inconsistent results. To more precisely evaluate their spermatogenesis effects, we investigated the correlation between the subdivided AZFc mutations and sperm production in 3,439 Han Chinese males. Our results showed that both partial AZFc deletion-only and primary duplication mutation presented a significant risk for decreased sperm production. Restoration of the reduced dosage of the AZFc content to the normal level had a milder effect, whereas an overdose of the AZFc content arising from multiple duplications of a partial AZFc-deleted structure produced a more serious consequence compared to the partial deletion-only mutation. Additionally, the AZFc-mutated structures with excessive NAHR-substrate showed a notably negative effect on spermatogenesis. These results suggest that the recurrent NAHR-based AZFc mutations may be associated with decreased spermatogenesis efficiency in present population. More significantly, our finding implies that the overdose of AZFc NAHR-substrate may produce an additional risk for the massive AZFbc deletions during the multi-stage division process of germ cells and thus impair the global spermatogenesis efficiency in the carriers.
Subject(s)
Chromosomes, Human, Y/genetics , Homologous Recombination , Spermatozoa/metabolism , Adult , Alleles , Asian People , Case-Control Studies , China , Chromosomes, Human, Y/chemistry , Deleted in Azoospermia 1 Protein , Gene Deletion , Gene Dosage , Haplotypes , Humans , Infertility, Male/genetics , Infertility, Male/pathology , Male , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Odds Ratio , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Spermatogenesis , Spermatozoa/cytologyABSTRACT
BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) after hepatectomy involves many factors. Previous studies have evaluated the separate influences of single factors; few have considered the combined influence of various factors. This paper combines the Bayesian network (BN) with importance measures to identify key factors that have significant effects on survival time. METHODS: A dataset of 299 patients with HCC after hepatectomy was studied to establish a BN using a tree-augmented naïve Bayes algorithm that could mine relationships between factors. The composite importance measure was applied to rank the impact of factors on survival time. RESULTS: 124 patients (>10 months) and 77 patients (≤10 months) were correctly classified. The accuracy of BN model was 67.2%. For patients with long survival time (>10 months), the true-positive rate of the model was 83.22% and the false-positive rate was 48.67%. According to the model, the preoperative alpha fetoprotein (AFP) level and postoperative performance of transcatheter arterial chemoembolization (TACE) were independent factors for survival of HCC patients. The grade of preoperative liver function reflected the tendency for postoperative complications. Intraoperative blood loss, tumor size, portal vein tumor thrombosis (PVTT), time of clamping the porta hepatis, tumor number, operative method, and metastasis were dependent variables in survival time prediction. PVTT was considered the most significant for the prognosis of survival time. CONCLUSIONS: Using the BN and importance measures, PVTT was identified as the most significant predictor of survival time for patients with HCC after hepatectomy.
